The objectives of this trial are: 1) To confirm the reponse rate to irinotecan in previously untreated colon cancers as >20%. 2) To characterize pharmacokinetic parameters of SN-38 and irinotecan 3) To characterize tumor samples for TOPO 1 activity 4) To determine the in vitro inhibition of TOPO 1 activity by irinotecan and SN-38 5) To determine the frequency of somatic mutations. Summary: Irinotecan has demonstrated impressive clinical activity against untreated and previously treated colon cancers. Response rates as high as 50% have been reported, although recent trials in the US indicated that the response rate will be closer to 25% in untreated patients and less than 20% in previously treated patients. Irinotecan is the first agent other than 5-fluorouracil to consistently demonstrate a measurable single agent response rate in metastatic colon cancer. This phase II trial is designed to optimize the clinical use of Irinotecan. We believe it important to conduct these studies in patients with measurable disease accesssible to biopsy for evaluation of biochemical predictors of response to understand the determinant of success or failure of this promising new therapy.